The Promotion of Physical Activity for the Prevention of Alzheimer's Disease in Adults with Down Syndrome

摘要 生活在美国的唐氏综合症（DS）患者人数从2000年的约50，000人增加到250，700人。 几乎所有患有DS的个体都显示与阿尔茨海默病（AD）相关的病理学 从30岁开始。先前在典型发育成人中的研究表明， 中度到剧烈的体力活动（MVPA）可以改善认知功能，并防止年龄相关的 大脑的结构和功能变化;然而，增加MVPA对大脑的潜在影响 尚未评估DS成人中AD的发展。尽管MVPA可能会产生积极影响， 认知和AD风险，年轻成年DS患者中MVPA的参与率较低。有限的研究 评估增加DS成人MVPA的策略，但在增加短- 术语（≤ 12周）或长期MVPA（12个月）。我们初步调查的结果（12周）这 在训练有素的健康教练的带领下，远程向家中患有DS的成年人群体提供实时MVPA （n=27），通过平板电脑上的视频会议显示出较高的出勤率， 小组会议和认知功能的改善。然而，可持续性，对每日总 MVPA，最佳会话频率，以及对远程认知功能和大脑健康的潜在影响 在患有DS的成人中提供的组MVPA会话是未知的。因此，我们建议12个月。早期 在80名患有DS的非痴呆成年人中进行的临床试验，以确定远程 提供组MVPA会话，以增加每日MVPA，相对于通常的护理控制。参与者将被 随机参加40分钟的低频率远程传递组MVPA会话（1会话/周，RL）， 高频（3次/周，RH）或常规护理对照。RL和RH臂的内容将是 除组会话频率（1 vs. 3/周）外，其余均相同。与资金来源一致 公告PAR-18-877本试验将评估RL，RH和 UC干预对MVPA的影响，并收集MVPA对认知和 与AD相关的脑健康在成年DS患者中。需要这些信息来告知 有充分把握度的晚期确证性试验，以评价增加MVPA预防或延迟 成人AD伴DS。我们的主要目的是评估基线时RL、RH和UC组的每日MVPA（min）， 3、6、9和12个月，并获得MVPA在12个月内变化的效应量。次要目标1将评估 MVPA在RL、RH和UC组中对心血管健康、生活质量、认知能力和 与AD相关的功能和脑参数（全脑和局部脑容量、功能连接、静息 状态MRI，脑血流）。第二个目标将确定可行性 RL、RH和UC组的保留率、会话出席率、记录会话的使用（仅RH/RL）和安全性。

Abstract The number of people with Down syndrome (DS) living the U.S. has grown from ~50,000 to ~250,700 over the past 70 yrs. Nearly all individuals with DS display pathology associated with Alzheimer's disease (AD) beginning as early as age 30. Previous research in typically developed adults suggests that increased moderate-to-vigorous physical activity (MVPA) may improve cognitive function and protect against age-related structural and functional changes in the brain; however, the potential impact of increased MVPA on the development of AD in adults with DS has not been evaluated. Despite the potential positive impact of MVPA on cognition and AD risk, participation in MVPA among young adults with DS is low. The limited research evaluating strategies for increasing MVPA in adults with DS and has been unsuccessful in increasing short- term (≤ 12 wks.) or long-term MVPA (12 mo.). Results from our preliminary investigation (12 wks.) which remotely delivers real-time MVPA, led by a trained health coach, to groups of adults with DS in their homes (n=27), via video conferencing on a tablet computer demonstrated high attendance, increased MVPA during group sessions, and improvements in cognitive function. However, the sustainability, impact on total daily MVPA, optimal session frequency, and potential impacts on cognitive function and brain health of remotely delivered group MVPA sessions in adults with DS are unknown. Therefore, we propose a 12 mo. early stage clinical trial in 80 non-demented adults with DS to determine the feasibility and potential efficacy of remotely delivered group MVPA sessions to increase daily MVPA, relative to a usual care control. Participants will be randomized to attend 40 min remotely delivered group MVPA sessions at a low frequency (1 session/wk.,RL), high frequency (3 sessions/wk., RH), or usual care control. Content for both the RL and RH arms will be identical with the exception of group session frequency (1 vs. 3/wk.). Consistent with the funding announcement PAR-18-877 this trial will assess the feasibility and potential effectiveness of the RL, RH, and UC interventions on MVPA, and gather initial estimates of the impact of MVPA on cognition and measure of brain health related to AD in adults with DS. This information is required to inform the development of adequately powered, late stage confirmatory trials to evaluate the role of increased MVPA to prevent or delay AD in adults with DS. Our primary aim will assess daily MVPA (min) in the RL, RH, and UC arms at baseline, 3, 6, 9, and 12 mos., and obtain effect sizes for change in MVPA over 12-mos. Secondary aim 1 will assess the impact of MVPA across the RL, RH, and UC arms on cardiovascular fitness, quality of life, cognitive function and brain parameters related to AD (whole and regional brain volume, functional connectivity, resting state MRI, cerebral blood flow) at baseline, 6, and 12 mos. Secondary aim 2 will determine the feasibility (retention, session attendance, use of recorded sessions (RH/RL only) and safety) of RL, RH, and UC arms.